Woman Delivers Baby After Ovarian Tissue Transplant

Procedure offers potential advancement in treatment of infertility due to disease tx

Action Points

Researchers reported the first case of fertility restoration after grafting of ovarian tissue removed and cryopreserved before menarche.

Live births have been reported after transplantation of cryopreserved ovarian tissue in adult patients, but the procedure remains unproven for ovarian tissue harvested at a prepubertal or pubertal age.

Researchers released the first-ever case report of a patient who carried a pregnancy to term after her ovaries were removed as a teenager and then reattached as an adult.

Isabelle Demeestere, of the Université Libre de Bruxelles in Belgium, and colleagues reported that a 27 year-old woman whose ovarian tissue was cryogenically preserved when she was 14 years of age had a successful ovarian graft and finally, more than 2 years later, a spontaneous pregnancy and the birth of a healthy baby.

This was the first instance of a live birth following transplantation of ovarian tissue that was harvested prior to a patient beginning menstruation, they wrote in Human Reproduction.

"This is an important breakthrough in the field because children are the patients who are most likely to benefit from the procedure in the future," said Demeestere in a statement. "When they are diagnosed with diseases that require treatment that can destroy ovarian function, freezing ovarian tissue is the only available option for preserving their fertility."

At age 13, the patient was diagnosed with a severe form sickle-cell anemia requiring treatment with hematopoietic stem cell transplantation (HSCT), and her parents opted for a cryopreservation procedure in an attempt to preserve her fertility during the treatment of her disease. A right oophorectomy via laparoscopy was able to remove 62 fragments of ovarian tissue, which were cryogenically preserved.

Following HSCT, the patient developed grade II acute graft-versus-host disease and limited chronic GVHD requiring treatment with immunosuppressive drugs for 18 months, the authors wrote. Due to this treatment, she developed primary ovarian failure with elevated gonadotropins, and her menstruation was induced via a third-generation estrogen-progesterone preparation at age 15.

When the patient wanted to become pregnant 10 years later, she was diagnosed with primary ovarian insufficiency with permanent amenorrhea and high gonadotropin levels. In an attempt to restore her fertility, two fragments of ovarian tissue consisting of two and six follicles per millimeter square were thawed and transplanted via a two-step laparoscopy.

Four thawed ovarian fragments were grafted on the residual left ovary, six were grafted in the right peritoneal bursa, and five were grafted subcutaneously using a trocar incision, the authors wrote.

Immediately following the grafting procedure, the patient experienced a decline in FSH serum level, but an increase in inhibin B and estradiol serum levels. But 4 months later, all hormonal levels had returned to the premenopausal range and a pelvic ultrasound revealed ovarian activity in the transplanted sites. The patient resumed menstruation 1 month after that.

Regular menstrual cycles resumed and for the next 2 years, basal FSH levels remained within normal range, while anti-Mullerian hormone (AMH) levels remained undetectable. She then underwent assisted reproductive technologies due to male infertility. More than 2 years following her transplantation, the patient then had a spontaneous pregnancy with a new partner and delivered a baby in November 2014 (birthweight 3140 g, Apgar score of 9 and 10 at 1 and 5 min, respectively).

Though not affiliated with the study, Alan Penzias, MD, of Boston IVF and director, Fellowship Program in Reproductive Endocrinology and Infertility at Harvard Medical School, called the efforts of the medical team "heroic and commendable" because there were no other options to preserve the patient's fertility, but pointed out the potential limitations of this highly experimental procedure.

"Tempering the excitement of this first report is the understanding that the efficiency with which strips of preserved ovarian tissue will successfully implant in host sites is unknown," he told MedPage Today via e-mail. "Strips of whole ovarian tissue may not survive the freeze and thaw process due to biophysical limits."

Demeestere also addressed potential ethical issues that may arise from this treatment in her statement, saying that it should not be used instead of hormone replacement therapy to induce menstruation and puberty in lower risk women.

"We think, at present, that cryopreserved ovarian tissue should be used only for fertility restoration in patients at high risk of ovarian failure, and not for puberty induction or for restoring menstrual cycles in adults," she said.

Still, they concluded that "this report offers, for the first time, evidence for the long-term survival of autografts of ovarian tissue cryopreserved before menarche and the efficiency of the procedure to restore fertility."

Penzias said that this report gives hope to women who have had ovarian tissue preserved prior to ablative chemotherapy, but this technique deserves further study.

"At present, preservation of strips of ovarian tissue for the purpose of restoring future menstrual function or fertility can only be considered an experimental last resort," he said. "It is a technique, among many others worthy of continued research."

The program was supported by the Fondation Belge contre le Cancer and the Fonds de la Rechere Scientifique FNRS-Télévie.

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.